Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.
Refolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells. Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-dist...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-02-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001268&type=printable |
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| author | Daniel Lamb Alexander W Schüttelkopf Daan M F van Aalten David W Brighty |
| author_facet | Daniel Lamb Alexander W Schüttelkopf Daan M F van Aalten David W Brighty |
| author_sort | Daniel Lamb |
| collection | DOAJ |
| description | Refolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells. Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-distal end of the trimer-of-hairpins that is strikingly conserved among divergent viruses. These asparagines are not essential for surface display of pre-fusogenic envelope. Instead, substitution of these residues dramatically disrupts membrane fusion. Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry. |
| format | Article |
| id | doaj-art-899a707dd69c4f9fa149105ecc6cce1e |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2011-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-899a707dd69c4f9fa149105ecc6cce1e2025-08-20T02:34:16ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-02-0172e100126810.1371/journal.ppat.1001268Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins.Daniel LambAlexander W SchüttelkopfDaan M F van AaltenDavid W BrightyRefolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells. Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-distal end of the trimer-of-hairpins that is strikingly conserved among divergent viruses. These asparagines are not essential for surface display of pre-fusogenic envelope. Instead, substitution of these residues dramatically disrupts membrane fusion. Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001268&type=printable |
| spellingShingle | Daniel Lamb Alexander W Schüttelkopf Daan M F van Aalten David W Brighty Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins. PLoS Pathogens |
| title | Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins. |
| title_full | Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins. |
| title_fullStr | Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins. |
| title_full_unstemmed | Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins. |
| title_short | Charge-surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins. |
| title_sort | charge surrounded pockets and electrostatic interactions with small ions modulate the activity of retroviral fusion proteins |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001268&type=printable |
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